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Lecture II. Layer of the Large Stellate Cells

Santiago Ramón y Cajal

Comparative Study Of The Sensory Areas Of The Human Cortex

By Santiago Ramón y Cajal

1899

My recent researches in the visual cortex of man have led to the unexpected discovery of certain large cells of stellate form possessing an axon which descends to the white matter. Figs. 9 and 10 represent very clearly the most common forms of these strange elements. They are differentiated immediately from pyramidal cells by their lack of a radial trimk. Generally speaking, the cell body is stellate, but there is no lack of semilunar, triangular, and even mitral forms. Their dendrites are thick and much branched, and extend in all directions, especially horizontally, without ever leaving the territory of the 4th layer. In man these processes are sparsely provided with contact granules, while they are very numerous in the homologous cells of the mammalia (cat and dog).

As to the axon, it is rather large, arises from the inferior surface of the cell body, descends through the 4th layer, sometimes tracing here accommodation curves, and after crossing the 6th, 6th, 7th and 8th layer, passes into the white matter and is there continued as a medullated nerve fibre. In passing through the 4th and 5th layers it gives off three, four, or a larger number of, often, very large collaterals which end in arborizations extending over a considerable area in these layers. It is not uncommon to see these collaterals taking a recurrent course to become distributed in planes above the point of origin ; but in this they never trespass on the boundaries of the 4th and 5th layers. Finally, and this is a very frequent disposition in the adult cortex, this axon, after having given off its collaterals, becomes notably finer. Taking into consideration its diameter, sometimes less than that of its first collateral, we might be led to mistake it for the latter rather than a true continuation of the axon. We shall return to this peculiarity, which is presented by many cells in the visual cortex. The stellate cells present a similar character in the adult human cortex, and I reproduce in Fig. 10 their principal types impregnated (long method of Golgi) in the case of a man thirty years old. The only difference that we remark between these cells in the adult and infant brain is the greater development of the dendrites, which extend long distances in horizontal planes in the adult. The volume of the soma also increases with age, which shows that growth of dendriU*s does not depend solely on the lengthening out of the initial or primitive protoplasm of the cell, but also on an actual augmentation of cell substance.

The cells with ascending axon are remarkable on account of the curious arched course of the latter. It has in some cases initial collaterals.

The stellate cells as well as other cells with the short axon are also found in the cortex of the cat and dog, where they form a well-defined layer of their own, corresponding, considering the character of its elements, to the 4th, 5th, and 6th in the visual cortex of the child, Fig. 12. Cells with short ascending axon are especially numerous and are characterized by being fusiform in shape and by the contact granules which cover the cell body and principal dendrites. Besides the existence of cells in the cerebral cortex whose axons ascend, but do not make their way into the first layer as do those from Martinotti's elements, is the fact that I long since discovered while working upon the motor cortex of the small mammals; this is, m my latest observations show, that these elements are very numerous, and that each cortical layer, or better, that each layer of a plexiform aspect, contains a special kind of this element. In addition, as we shall see in a moment, these cells form a constant factor in all the cortical layers in which nerve fibres incoming from the white matter make their terminal arborizations.

Fifth Layer, or Layer of Small Stkllats Cells

This layer, which corresponds to the greater part of the stripe of Vicq d*Azyr, when examined in Nissl preparations appears to contain an enormous number of small rounded elements which might be mistaken for scattered nuclei not surrounded by protoplasm. But in these same preparations we may still detect, beside these corpuscles, a few others, scattered here and there, of stellate or triangular form and medium or large size, very similar to the great stellate cells of the 4th layer. 6olgi*s method reveals to us the great complexity of the 5th layer, and by this means we have succeeded in differentiating as many as five kinds of elements. The following are the most common types : —

(a) SuUaU CelU of Medium SiMe. — These are exactly similar to the stellate cells of the 4th layer. They are not numerous, and lie irregularly scattered in all levels of the 6th layer. Their dendrites diverge, but run for the most part horizontally, and do not pass beyond the layer of their cells of origin. Their axons descend and, after emitting a few collaterals to the 5th layer, make their way to the white matter. In some cases their collaterals are given off lower down, in the 6th layer, and then their course is recurrent, because they must make their terminal arborizations between homonymous cells (Fig. 9, ^r,/).

(b) CelU with Aieendinff Aixm. — These are fusiform or triangular, disposed with long axis vertical. Their axon is similar to that of cells of this type in the 4th layer. That is to say, after ascending a certain distance it forms a terminal arborization of arching branches distributed among the elements of the overlying layer. From its initial portion spring a few collaterals which are distributed to the 5th layer (Fig. 13, A, B, C).

(c) Ovoid or SullaU Corpu$eU$ (properly dengnaUd^ QranuUi). — These rarely exceed in diameter more than ten or twelve /ft. They are the most numerous element of the 5th layer. Their soma is ovoid^ spheroidal, and even polygonal in form and gives rise to three, four, or more fine, smooth dendrites, which terminate, after a short, wavy course, within the limits of the 6th layer. Their axons are very delicate and take a great variety of directions, — ascending, descending, or horisontal, — and finally end in an extended arborization of few branchlets distributed exclusively to the very midst of the 6th layer (Fig, 14).

(d) Ihoarf or Spider^Juiped Carpuiele$. — Of these there is no lack in this layer, whose nerve plexus they help to bewilder. Their very tiny, often ascending, axon resolves itself very soon into an extremely dense, fine arborization close to the cell. In the dense masses of these arborizations we notice spaces, which probably correspond to groups of granules.

Fig. 15. — Cells with short axons of the layer of stellate cells from the Tisaal cortex of a cat aged 28 days, a, large cell whose descending axon snbdiyides in the deeper level of the 4th layer (4th and 5th of man) ; 5, arachniform cell whose axon forms a fine and very dense plexns; d, fusiform cell whose axon is resolved into vertical branches.

The cells with short axons are very abundant in the visual cortex of the cat, as may be observed by examining Figs. 15 and 16. Among them the more abundant types are : a, fusiform cells whose ascending axon is distributed to the superior levels of the layer in question (4th and 5th in man) (Fig. 16, 2>); &, large stellate cells with descending axon forming their terminal arborizations in the deeper levels of this layer (Fig. 15, a);

Nerve Plexus of the 5th and 6th layere of the Cortex. One of the chief characteristics of these layers consists in the very dense plexus of medullated fibres extending among their nerve cells. This is formed by two kinds of fibres : (1 ) Exogenous fibres, that is to say those coming from the white matter, probably continuations of the cerebro-optio tract. (2) Endogenous fibres, formed by the terminal arborizations of the axons which come from cells of the 4th and 5th or the underlying layers.

Exogenous Fibres. — I have already stated that Gennari's or Yicq d'Azyr's stripe corresponds chiefly to the 5th layer, but also includes part of the 4th. However, the true composition of this stripe cannot be seen in Weigert-Pal preparations, because the hematoxylin stains only the large or medium-sized fibres which possess a myeline sheath. Now these fibres, as we shall presently see, represent but a very small portion of the components of Gennari's stripes. Very fortunately Golgi's method, applied to the brain of an infant at birth or but a few days old, affords us a veiy clear view of the meduUated and unmedullated fibres which make up this plexus. This method accordingly furnishes us a means of analyzing its origin and manner of termination. Permit me to state at the outset that the principal contingent of exogenous fibres is represented by a consid« erable number of fibres from the white matter, which I shall henceforth call, in virtue of their physiological significance, optic fibres.

The optic fibres are easily distinguished from the axons of the pyramids by their direction, which is oblique (in some cases they are tortuous or even stair-shaped), by their large calibre, often exceeding that of axons of the giant pyramids ; finally by the fact that, instead of going to a cell as its axon, they repeatedly divide dichotomously, each branch resolving itself into a perfectly free terminal arborization spreading almost horizontally through the extent of the 4th and 5th layers. Fig. 17 reproduces the appearance of the optic plexus in a preparation in which it was impregnated almost alone. I call your attention to the fact that these optic fibres send off no collaterals, or very few, in passing through the deeper layers (9th, 8th, 7th, 6th), but immediately on reaching the 5th layer their final ramification begins. This occurs in many ways. Some fibres divide at different levels of the 5th layer into two equal or unequal branches which run horizontally to great distances, becoming resolved into a great number of collaterals which ramify throughout the entire thickness of the layer. Other fibres may be seen which, after giving off a few long collaterals during their ascent through the 6th layer, reach up to the extreme limit of the 5th layer and here become horizontal. There is no lack of fibres which ascend directly up to the limit of the layer of medium-sized pyramids and there describe arcs, and even very long wavy courses, and end by descending, dividing as they descend, through the 4th and 5th layers. Finally, from the arching portion of some of these latter fibres fine coUat

enb may be seen to spring on their way to the layer of medium-sized pyrramids, where they disappear after a few divisions. To sum up, the optio fibres terminate almost exclosiYely within the 4th and 5th layers. In only two instances have I discovered collaterals of optic fibres which appeared to form their terminal arborizations within the 1st layer.

This plexns of optic fibres is one of the richest and densest to be found in the gray matter of the brain. If it b completely impregnated, which frequently occurs in an infant brain fifteen or twenty days old, it appears as a be* wildering meshwork of wavy fibres, besprinkled with vacant spaces corresponding to the cell bodies of these layers (Fig. 18, B).

I may add that the appearance of this plexus diffres a little in the two layers (Fig. 18). In the 4th layer its fibres are larger and often disposed in arches or horizontal bars, its arborizations are loose and separated by ample spaces in conformity to the size of the great stellate cells; while in the 5th layer it consists of fine varicose fibrils arranged in an extremely dense lattioe work with small spaces corresponding to the small size of the medium-sized stellate cells (Fig. 18, 5).

In the preceding brief description I have called the large exogenous fibres optic fibres. But what reasons have we to suppose that these fibres actually come in from the primary optic centres? We must acknowledge, at the outset, that the proof of their optical origin is not perfect ; but there is no lack of facts which favor such a view. Some of these facts are the following : —

(a) In the minute brains, as, for example, that of a newborn mouse, we can follow these fibres in some cases to the radiation of Gratiolet.

(b) The fibres which are on their way to Gennari's plexus are very large, larger than the axons of the giant pyramids or those of cells of intercortical association.

(c) In the motor cortex we have found that large fibres distributed in a similar way actually come in from the corona radiata.

(c?) In the visual cortex of a man who became blind I have discovered, by using Nissl's method, a perceptible atrophy of the stellate cells of the 4th and 5th layers. A similar case has been recently reported by Cramer ; and this fact would seem to point to an intimate union between these elements and the act of visual perception, a union whose material bond is probably represented by the exogenous fibres of Gennari's plexus.

(jr) Granted that the visual cortex must receive a great number of fibres from the radiation of Gratiolet, it is natural to refer to this source the fibres which form Gennari's plexus ; since this is the distinctive plexus of this region of the brain.

From the probable fact that the plexus of Gennari's stripe is the terminus of the optic fibres, we may draw the important conclusion that the cells of the 4th and 5th layers represent histologically the principal substratum for visual sensation ; because up to this point in the cortex sensory impulses heap up on the centripetal side, and here begin to become centrifugal.

Another conclusion not less interesting follows from it : for an ensemble of anatomico-physiological facts seem to show that the region of the calcarine fissure is not the locus of visual memories, but only that of sensations of luminosity, and that the residues of the latter must go (in order to become transformed into latent images) to other nerve centres. We are naturally led to consider the long axon of the 4th and 5th layers as the principal, if not the only, path joining these two kinds of centres.

These fibres would function, accordingly, in carryring the copy, or the sensory residue, received in Gennari's plexus, to appropriate association areas of the brain. Their psychic role is thus a very important one, and we should suppose that their interruption would produce psychic blindness as certainly as the destruction of the occipital lobe itself.

The plexus of Gennari is well developed in other mammals, but the terminal arborizations are never as complicated as in man (Fig. 19). Further than this I have not been able to demonstrate any definite differences in arrangement at various levels of the layer of stellate cells. However, it has seemed to me that the terminal branches, which are very varicose, tend to be especially dense in the superficial planes of this layer.

Endogenous Fibres

In addition to the large nerve fibres entering from the white matter, Gennari's plexus contains either terminal or collateral ramifications of fibres which arise in the cells proper of the visual cortex. Such are : —

The very numerous branches from the small cells with short axon of the 6th layer.

The terminal neuritic arborizations of cells with ascending axon lying in the 6th, 7th, and 8th layers.

Arborizations of collateral branches supplied to the 4th and 5th layers by the long descending axons of the stellate cells.

Terminal arborizations from the fusiform or triangular cells of the 4th and 5th layers which have ascending axons, etc.

The plexus formed by all the above fibrils is usually finer than that of the optical fibres. In order to make out to the best advantage its extreme complication throughout its whole extent, we must study it in the cortex of an infant from fifteen to twenty-five days old, a period at which the terminal arborizations of the visual cells are completely developed. It has seemed to me that the endogenous arborizations are more numerous in the 4th than in the 5th layer. We may notice also that they show a tendency to form true nests surrounding the stellate cells of these two median layers.

Sixth Layer

Plexif orm and poor in cells in Nissl preparations, it contains a large number of small pyramidal or ovoid elements with long axis vertical and provided, as may be seen in good Golgi specimens, with a radial trunk extending up to the first layer. They have also a few short basilar dendrites, descending or oblique and little branched. But the most distinctive character of these small elements consists in the course of their axons. These descend a short distance, then curve upward and ascend through the 6th, 5th, and 4th layers, to which they give a few collaterals, and end in a manner which I have not been able to discover. In some cases these axons have branched close to their origin and, instead of one, describe two arcs continued by ascending fibres. Other axons, moreover, make even a greater number of loops. From the convex aspect of these curves, as well as from the ascending portion of the axons, within the 6th layer spring numerous collaterals which branch throughout the entire thickness of the layer. Some descend still further and subdivide in the plexus of the 7th layer, that is to say, at the level of the giant pyramids (Fig. 20, -B).

Besides these small cells, which are certainly the most abundant, we find two other cellular types : (a) Cells of stellate form and medium size. They possess radiating dendrites which do not usually pass beyond the 6th layer. Their axons ascend and form an arborization throughout the extent of the 6th, 6th, and 4th layers. (V) Ordinary pyramidal cells, very scarce, of medium or large size. They have precisely the same characters as the pyramids of the 7th layer.

Seventh Layer or Layer of Giant Pyramids

Solitary Cells of Meynert. — This layer contains one or two irregular and discontinuous files of giant pyramids, which appear, here and there, lost as it were in a dense and extended plexus. To this plexus the layer owes its finely granular appearance, which may be seen even in preparations stained by Nissl's method (Fig. 20, (7, and Fig. 22, B).

The cells in question, like other pyramidal cells, possess a very large radial trunk which ends in a flattened spray of horizontal branches in the lower levels of the plexiform layer. The cells are also provided with a few many-branched basilar dendrites which distribute themselves throughout the layer and, finally, with a great number of horizontal dendrites forming a plexus which would seem to provide connections between these cells through long distances. This is such a characteristic feature that by its presence alone we are able to distinguish the visual from all other cortical areas. The axon of the giant pyramids is very large, extends almost vertically through the 8th and 9th layers, and is continued as a fibre of the white matter. Collaterals spring from its initial portion which ramify in the 7th and even the superficial levels of the 8th layer.

numerous, the 7th layer contains : (a) a number of medium-sized pyramids possessing the same characters ; (() seyeral small elements exactly similar to those of the 6th layer, the cells with the complicated forked and arched axons distributed in the manner aboye described (Fig. 20, K^uJ); (O in addition may be found medium-sized stellate cells situated in the 7th and 8th layers (Fig. 21, A^ B). The very remarkable feature of the latter cells consists in their terminal arborizations. Their neurites take at first an ascending or oblique course, divide into two, and then give rise to a large number of oblique or horizontal branches which occupy a good part of the 7th layer. In the brain at birth their terminals present no special peculiarities ; but in one twenty days old I have found that a number of these arborizations surround the giant pyramids, forming terminal nests. Only their arrangement is not so definite here as in the motor region, where we find it wonderfully developed. (Compare with description below.)

Eighth Later

Examined in Nissl preparations this layer presents a mass of mediomsized pyramids and a remarkably dense formation of granules. This is the reason Meynert and other writers have called this the layer of deep granules or inferior granular layer.

Golgi's method reveals in this formation elongated oells of pyramidal form. They have the radial trunk continued, up to the pleziform layer and also descending basilar dendrites which become subdivided and end within the 8th layer. Among these there is no lack of fusiform or triangular cells, but they always present the long radial trunk which we find over the whole cortex (Fig. 22, (7).

In general form, it will be observed that these cells resemble true pyramids. However, the peculiar behavior of their axons establishes a very clear distinction between them. As may be seen in the figure (22, i), this axon at first descends, then describes an arc, ascends into the 7th, 6th, and 5th layers, and finally ends in a horizontal arborization chiefly distributed to the layer of stellate cells, but a few of its branches go to the 5th layer. From the loop of the axon, and in the course of its ascent, spring several collaterals, which ramify in difiFerent planes of the 8th layer. In a few of these cells we may observe that, at the bend of the axon, a slender branch, similar to a collateral, is given off, which crosses the 8th and 9th layers and enters the white matter as a meduUated fibre (Fig. 22, g). The great majority of these collaterals, however, terminate completely within the 8th and 9th layers. At any rate, we must distinguish, considering the morphology of their axons, two kinds of cells : (a) oells with arched axon none of whose collaterals extend to the white matter ; (() cells whose neurite divides, at the arch, into a fine descending branch, which becomes a medullated fibre of the white matter, and into a larger ascending branch with its terminal arborization in the 4th or 5th layers.

This arched arrangement of the axon in cells of the 8th layer appears very strange. It occurs not only in the infant brain, but in the visual cortex of the adult as well. It seems, at first sight, to violate aU laws that govern the length and direction of the axons in other sections of the nervous system. And, what seems still more remarkable, all these whimsical windings seem to subserve solely the purpose of shortening the stretch between the cell body and the first ooUaterals given off by the aroh. This same phenomenon occurs in many other nerve cells. Were it not for a deviation from our present theme, I might add noe yery convincing instances of this tendency of the axon to take the direction meet favorable for the nerve impulses which arise in the cell to very quickly reach the elements connected with their initial collaterals.

Permit me also to add that the 8th layer contains giant stellate cells with ascending axon (Martinotti's cells), which runs to the plexiform layer (Fig. 22, j), and also a similar but smaller cell, whose axon gives rise to an arborization between the neighboring cells.

Ninth Layer

Coinciding closely with the so-called polymorphic layer of other authors, this layer contains elongated elements, fusiform, triangular, or ovoid, possessing a radial dendrite, extending up to the plexiform layer, and also one or several basal dendrites, which take a descending or oblique direction. Finally, these cells have an axon which descends in a straight line to the white matter; where, after giving off several collaterals, it continues as a medullated fibre. There are also in the 9th layer a few fusiform cells with short radial dendrites and ascending axon and a number of stellate cells with short axon of the so-called Golgi type.

In addition, the arrangement of the cells of the 9th layer varies greatly in different parts of a convolution. In the convex portion they are very numerous, fusiform, and slender, elongated and perfectly radial ; while opposite the sulcus they have a quite different form, are stouter, more variable, and frequently lie with long axis parallel to the white matter, i.e. perpendicular to their ordinary direction. Their peripheral processes perform the most whimsical contortions in order to become radial and reach the plexiform layer. Their axon appears frequently horizontal, describing a very open curve on its way to the white matter. All these forms and many others represent adaptations of the cells to the foldings of the cortex and to its varying thickness in different parts of a convolution.

I will not impose further upon your indulgent attention with these tiresome enumerations of layers and forms of cells, in the mazes of which nature herself seems to have intended to lose the investigator and put his patience to the test. And I will close this tedious lecture with a succinct exposition of the anatomico-physiological inductions that seem to follow from my observations on the minute structure of the visual cortex of man and the mammalia.

The visual cortex of man and gyrencephalous mammals possesses a special structure very different from that of any other cortical area.

The visual region is characterized, above all, by fewness of giant pyramids and by presenting, at the level of the granular layer of other cortical areas, three distinct layers of cells of special form, to wit : the layer of large stellate cells, the layer of small stellate cells, and the layer of pyramids with arched ascending axon.

Since these optic fibres are distributed chiefly to the stellate cells of the 4th and 5th layers, it seems natural to consider these elements the substratum of visual sensation.

The innumerable cells with short axons in the 4th and 6th layers represent, probably, the intermediate links between the optic fibres on the one side and the stellate cells of the 4th and 5th layers and the pyramidal cells on the other.

As these intermediate cells are often very small and have short axons, it may be that, besides their function of diffusing the incoming impulses through the cortex, they play also the special role of augmenting the visual impulses by fresh discharges of nerve force, in order that they may reach, in sufficient strength, the cortical regions in which the function of commemorative recording of optical images occurs. The pathways for conveyance of visual residues from the median occipital region to the association centres in the parietal cortex are possibly represented by axons of the stellate cells of the 4th and 5th layers.

Granting that the giant pyramids of other cortical regions give rise to motor fibres, it would follow that in the 7th layer they possess the same function. These cells, whose dendritic trunks come into contact with the optical plexus, 4th and 5th layers, serve probably to mediate the reflexes of the eyeball and head (conjugate movements of the eyes) occasioned by elective stimulation of the visual cortex, a theory which would seem to be supported by the physiological experiments of Schafer, Danillo, Munk, and others.

Granting that each giant pyramid oomes into contact in the 4th and 6th layers, as well as in the first layer, with fibres that are probably associative, we may suppose that motor discharges of these cells can be effected by two kinds of impulses : by ordinary optical stimulation and by stimuli of a yolitional order, possibly coming from the association centres and reaching, finally, the plexiform layer.

My own researches do not furnish grounds for further conclusions. Many points still remain to be cleared up; but their complete elucidation will be the fruit of researches more detailed and exact than those I have been able to undertake.

Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding. (More? Embryology History | Historic Embryology Papers)